Tina Wu, Ph.D.

The human breast cancer microenvironment displays features of T helper 2 (Th2) immunity, which promotes tumor development. We showed that breast cancer cell-derived thymic stromal lymphopoietin (TSLP), by inducing OX40L expression on DCs, contributes to the Th2 immunity conducive to breast tumor development. In order to reprogram the inflammatory pro-tumor Th2 (iTh2) into anti-tumor Th1 microenvironment, we tested the impact of targeting the innate receptors on DCs to render the resistant to tumor environment. We show that intratumoral delivery of β-glucan, a natural ligand for dectin-1 expressed on DCs, blocks the generation of iTh2 cells leading to decreased IL-13 in the tumor microenvironment and prevents breast cancer development. β-glucan exposed DCs expand CD8+ T cells, which produce higher IFNg, Granzyme A and Granzyme B, accumulate in the tumors leading to enhanced tumor necrosis in vivo. Our data demonstrate that exploiting pattern-recognition receptors on tumor-infiltrating DCs enables cancer rejection. We are further exploring the ATACseq and RNAseq approach to understand the regulation of TSLP production in breast tumor cells and how TSLP alters the infiltrating DCs. It can be novel molecular biology approaches to decode tumor infiltrating DCs and T cells and define potential targets for immunotherapy.

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